1. Field
Provided are an anti-c-Met/anti-EGFR/anti-HER3 multispecific antibody, and a method of preventing and/or treating a cancer using the same.
2. Description of the Related Art
c-Met and EGFR proteins interact with each other and are involved in various mechanisms related to tumors. These proteins (targets) are typical receptor tyrosine kinases (RTKs) present at the surface of cells, capable of inducing the proliferation of cancer cells, the penetration of the cancer cells, angiogenesis, etc. Also, these proteins participate in each other's signal transduction systems by interacting with each other, thereby inducing resistance against each other's therapeutic agents.
The EGFR family comprises EGFR (HER1), HER2 (Erbb2), HER3 (Erbb3) and HER4 (Erbb4), and forms a homodimer or a heterodimer to mediate signal transduction. Inhibiting the signal is important to cancer development and growth. If resistance to anti-EGFR family or anti-c-Met therapy is developed, HER3 may be activated to exert signal transduction, thus, it is hardly expected to yield a satisfactory therapeutic result.
Multispecific antibodies targeting two or more antigens have been developed in various kinds and forms and are expected as a new drug antibody having excellent therapeutic effects compared to a monoclonal antibody. Most of multispecific antibodies have been developed so that their therapeutic effects on cancers can be increased by recognizing an antigen of cytotoxic cells (killer cells) and other antigen of cancer cells at the same time thus allowing the cancer cells to be killed by the cytotoxic cells. However, research in the field indicates that cancer cells themselves can be mutated to proliferate and penetrate even by intracellular ligands or various antigens of the same cancer cells other than the targeted antigen, it is expected that a multispecific antibody capable of recognizing another antigen of the cancer cells as well as an antigen of the killer cells will be also useful in treating cancers.
In addition, various multispecific antibodies have been developed, but their efficiency was not proved in clinical tests or several side effects were observed. For these reasons, there were many cases which were not approved by FDA and were not marketed as therapeutic antibodies. One of the biggest reasons for which, in spite of the fact that multispecific antibodies having various forms and mechanisms have been developed, the multispecific antibodies were not marketed, is a problem in the stability and productivity of the antibodies. In the production of early multispecific antibodies having an IgG form, random combination of light chains and heavy chains of the antibodies, made it very difficult to separate and purify the desired kind of multispecific antibodies, providing an obstacle to mass production. Also, in case of multispecific antibodies with other than IgG forms, their stabilities as a drug were not verified in fields such as protein folding, pharmacokinetics, and the like.
Accordingly, there is a need for the development of a multispecific antibody which is predicted to achieve effective cancer treatment effects by recognizing two or more kinds of antigens in cancer cells at the same time. Furthermore, there is a need for the development of a bispecific antibody which can enhance cancer treatment as well as solve the side-effect and resistance problems of existing cancer treatment regimens.